Thisresearch program proposes to study the biophysical propertiesand subunit interactions of voltage gated K+ channels and their roles in the physiology of T Lymphocytes. Specifically, we will determine the physiological impact of irreversibly ablating specific endogenous K+ channel isoforms in primary human T cells on membrane potential, regulatory volume decrease, interleukin-2 secretion, cell proliferation and apoptosis (programmed cell death). Additionally, we will determine turnover rates of functional channels and K+ channel mRNA steady-state levels to assess T cell responses to elimination of K+ current. We have chosen to use a molecular laser ablation technique, chromophore laser assisted inactivation (CALI), which has been developed by Dr. Daniel Jay of Harvard University.